Pronuciferine and nuciferine inhibit lipogenesis in 3T3-L1 adipocytes by activating the AMPK signaling pathway

• Published in: Life sciences (1973) 2015-09, Vol.136, p.120-125
• Main Authors: Ma, Chengjun, Li, Gang, He, Yanfeng, Xu, Bo, Mi, Xiangquan, Wang, Honglun, Wang, Zhenhua
• Format: Article
• Language: English
• Subjects: 3T3-L1 adipocytes; 3T3-L1 Cells; Adipocytes - drug effects; Adipocytes - metabolism; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Anti-Obesity Agents - pharmacology; Aporphines - pharmacology; Drug Evaluation, Preclinical; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; Lipid Droplets - metabolism; Lipogenesis; Lipogenesis - drug effects; Mice; Nuciferine; Pronuciferine; Signal Transduction - drug effects; Spiro Compounds - pharmacology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2015.07.001

Nelumbo nucifera (Gaertn.) leaves are used widely in modulating obesity in traditional Chinese medicine. Our previous work demonstrated that aporphine alkaloids from it increased the glucose consumption in mature 3T3-L1 adipocytes. However, the underlying mechanisms of this increase remain unclear. Here we investigated the modulating effects of pronuciferine and nuciferine on lipogenesis and glucose uptake in insulin resistant 3T3-L1 adipocytes in vitro. Insulin resistant 3T3-L1 mature adipocytes were induced with dexamethasone, 3-isobutyl-methylxanthine and insulin. The lipid droplets and the intracellular triglyceride contents in mature adipocytes were detected by Oil red O staining and colorimetry respectively. The glucose uptake was measured with a fluorescent deoxyglucose analog (2-NBDG). The glucose transporter type 4 (GLUT-4) expression was measured by fluorescent-immunohistochemistry and the activation of 5′-AMP-activated protein kinase (AMPK) was detected by its alpha subunit phosphorylation. Both nuciferine and pronuciferine treatments significantly decreased the lipid droplets and the intracellular triglyceride contents but increased the glucose uptake in the insulin resistant 3T3-L1 adipocytes. Furthermore, both pronuciferine and nuciferine showed the ability to up-regulate the expression of GLUT4, triggering the phosphorylation of AMPK in mature 3T3-L1 adipocytes, although pronuciferine exhibited a more powerful effect compared to nuciferine. In summary, all the results demonstrate that pronuciferine and nuciferine ameliorate the glucose and lipid metabolism in insulin-resistant 3T3-L1 adipocytes, which might be due to the activation of the AMPK signaling pathway.